Boston’s NPR station, 90.9 WBUR, ran a story this morning about cutting edge dyslexia research as part of their series called “Brain Matters.” They featured John Gabrieli’s brain imaging research, which found differences in a key language structure, even before children start learning to read.
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Is this the golden age of neuroscience?
Today, WBUR (Boston’s NPR station) began a 2-month long series on the brain called “Brain Matters.” This morning, they ran a segment which featured interviews with Bob Desimone and Ed Boyden. Desimone was also the featured guest on the Radio Boston, where he fielded questions from callers about the current state of brain research.
As part of this series, WBUR.org posted 12 images that show some of the cutting-edge techniques that scientists are using to try to solve the mystery of the brain. Some of the beautiful images are from McGovern labs. “Brain Matters” also asked 11 young neuroscientists from BU, Harvard and MIT to share what they’re working on — and why their research is important. These interviews are posted on the WBUR website.
When good people do bad things
When people get together in groups, unusual things can happen — both good and bad. Groups create important social institutions that an individual could not achieve alone, but there can be a darker side to such alliances: Belonging to a group makes people more likely to harm others outside the group.
“Although humans exhibit strong preferences for equity and moral prohibitions against harm in many contexts, people’s priorities change when there is an ‘us’ and a ‘them,’” says Rebecca Saxe, an associate professor of cognitive neuroscience at MIT. “A group of people will often engage in actions that are contrary to the private moral standards of each individual in that group, sweeping otherwise decent individuals into ‘mobs’ that commit looting, vandalism, even physical brutality.”
Several factors play into this transformation. When people are in a group, they feel more anonymous, and less likely to be caught doing something wrong. They may also feel a diminished sense of personal responsibility for collective actions.
Saxe and colleagues recently studied a third factor that cognitive scientists believe may be involved in this group dynamic: the hypothesis that when people are in groups, they “lose touch” with their own morals and beliefs, and become more likely to do things that they would normally believe are wrong.
In a study that recently went online in the journal NeuroImage, the researchers measured brain activity in a part of the brain involved in thinking about oneself. They found that in some people, this activity was reduced when the subjects participated in a competition as part of a group, compared with when they competed as individuals. Those people were more likely to harm their competitors than people who did not exhibit this decreased brain activity.
“This process alone does not account for intergroup conflict: Groups also promote anonymity, diminish personal responsibility, and encourage reframing harmful actions as ‘necessary for the greater good.’ Still, these results suggest that at least in some cases, explicitly reflecting on one’s own personal moral standards may help to attenuate the influence of ‘mob mentality,’” says Mina Cikara, a former MIT postdoc and lead author of the NeuroImage paper.
Group dynamics
Cikara, who is now an assistant professor at Carnegie Mellon University, started this research project after experiencing the consequences of a “mob mentality”: During a visit to Yankee Stadium, her husband was ceaselessly heckled by Yankees fans for wearing a Red Sox cap. “What I decided to do was take the hat from him, thinking I would be a lesser target by virtue of the fact that I was a woman,” Cikara says. “I was so wrong. I have never been called names like that in my entire life.”
The harassment, which continued throughout the trip back to Manhattan, provoked a strong reaction in Cikara, who isn’t even a Red Sox fan.
“It was a really amazing experience because what I realized was I had gone from being an individual to being seen as a member of ‘Red Sox Nation.’ And the way that people responded to me, and the way I felt myself responding back, had changed, by virtue of this visual cue — the baseball hat,” she says. “Once you start feeling attacked on behalf of your group, however arbitrary, it changes your psychology.”
Cikara, then a third-year graduate student at Princeton University, started to investigate the neural mechanisms behind the group dynamics that produce bad behavior. In the new study, done at MIT, Cikara, Saxe (who is also an associate member of MIT’s McGovern Institute for Brain Research), former Harvard University graduate student Anna Jenkins, and former MIT lab manager Nicholas Dufour focused on a part of the brain called the medial prefrontal cortex. When someone is reflecting on himself or herself, this part of the brain lights up in functional magnetic resonance imaging (fMRI) brain scans.
A couple of weeks before the study participants came in for the experiment, the researchers surveyed each of them about their social-media habits, as well as their moral beliefs and behavior. This allowed the researchers to create individualized statements for each subject that were true for that person — for example, “I have stolen food from shared refrigerators” or “I always apologize after bumping into someone.”
When the subjects arrived at the lab, their brains were scanned as they played a game once on their own and once as part of a team. The purpose of the game was to press a button if they saw a statement related to social media, such as “I have more than 600 Facebook friends.”
The subjects also saw their personalized moral statements mixed in with sentences about social media. Brain scans revealed that when subjects were playing for themselves, the medial prefrontal cortex lit up much more when they read moral statements about themselves than statements about others, consistent with previous findings. However, during the team competition, some people showed a much smaller difference in medial prefrontal cortex activation when they saw the moral statements about themselves compared to those about other people.
Those people also turned out to be much more likely to harm members of the competing group during a task performed after the game. Each subject was asked to select photos that would appear with the published study, from a set of four photos apiece of two teammates and two members of the opposing team. The subjects with suppressed medial prefrontal cortex activity chose the least flattering photos of the opposing team members, but not of their own teammates.
“This is a nice way of using neuroimaging to try to get insight into something that behaviorally has been really hard to explore,” says David Rand, an assistant professor of psychology at Yale University who was not involved in the research. “It’s been hard to get a direct handle on the extent to which people within a group are tapping into their own understanding of things versus the group’s understanding.”
Getting lost
The researchers also found that after the game, people with reduced medial prefrontal cortex activity had more difficulty remembering the moral statements they had heard during the game.
“If you need to encode something with regard to the self and that ability is somehow undermined when you’re competing with a group, then you should have poor memory associated with that reduction in medial prefrontal cortex signal, and that’s exactly what we see,” Cikara says.
Cikara hopes to follow up on these findings to investigate what makes some people more likely to become “lost” in a group than others. She is also interested in studying whether people are slower to recognize themselves or pick themselves out of a photo lineup after being absorbed in a group activity.
The research was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the Air Force Office of Scientific Research, and the Packard Foundation.
Inside the adult ADHD brain
About 11 percent of school-age children in the United States have been diagnosed with attention deficit hyperactivity disorder (ADHD). While many of these children eventually “outgrow” the disorder, some carry their difficulties into adulthood: About 10 million American adults are currently diagnosed with ADHD.
In the first study to compare patterns of brain activity in adults who recovered from childhood ADHD and those who did not, MIT neuroscientists have discovered key differences in a brain communication network that is active when the brain is at wakeful rest and not focused on a particular task. The findings offer evidence of a biological basis for adult ADHD and should help to validate the criteria used to diagnose the disorder, according to the researchers.
Diagnoses of adult ADHD have risen dramatically in the past several years, with symptoms similar to those of childhood ADHD: a general inability to focus, reflected in difficulty completing tasks, listening to instructions, or remembering details.
“The psychiatric guidelines for whether a person’s ADHD is persistent or remitted are based on lots of clinical studies and impressions. This new study suggests that there is a real biological boundary between those two sets of patients,” says MIT’s John Gabrieli, the Grover M. Hermann Professor of Health Sciences and Technology, professor of brain and cognitive sciences, and an author of the study, which appears in the June 10 issue of the journal Brain.
Shifting brain patterns
This study focused on 35 adults who were diagnosed with ADHD as children; 13 of them still have the disorder, while the rest have recovered. “This sample really gave us a unique opportunity to ask questions about whether or not the brain basis of ADHD is similar in the remitted-ADHD and persistent-ADHD cohorts,” says Aaron Mattfeld, a postdoc at MIT’s McGovern Institute for Brain Research and the paper’s lead author.
The researchers used a technique called resting-state functional magnetic resonance imaging (fMRI) to study what the brain is doing when a person is not engaged in any particular activity. These patterns reveal which parts of the brain communicate with each other during this type of wakeful rest.
“It’s a different way of using functional brain imaging to investigate brain networks,” says Susan Whitfield-Gabrieli, a research scientist at the McGovern Institute and the senior author of the paper. “Here we have subjects just lying in the scanner. This method reveals the intrinsic functional architecture of the human brain without invoking any specific task.”
In people without ADHD, when the mind is unfocused, there is a distinctive synchrony of activity in brain regions known as the default mode network. Previous studies have shown that in children and adults with ADHD, two major hubs of this network — the posterior cingulate cortex and the medial prefrontal cortex — no longer synchronize.
In the new study, the MIT team showed for the first time that in adults who had been diagnosed with ADHD as children but no longer have it, this normal synchrony pattern is restored. “Their brains now look like those of people who never had ADHD,” Mattfeld says.
“This finding is quite intriguing,” says Francisco Xavier Castellanos, a professor of child and adolescent psychiatry at New York University who was not involved in the research. “If it can be confirmed, this pattern could become a target for potential modification to help patients learn to compensate for the disorder without changing their genetic makeup.”
Lingering problems
However, in another measure of brain synchrony, the researchers found much more similarity between both groups of ADHD patients.
In people without ADHD, when the default mode network is active, another network, called the task positive network, is suppressed. When the brain is performing tasks that require focus, the task positive network takes over and suppresses the default mode network. If this reciprocal relationship degrades, the ability to focus declines.
Both groups of adult ADHD patients, including those who had recovered, showed patterns of simultaneous activation of both networks. This is thought to be a sign of impairment in executive function — the management of cognitive tasks — that is separate from ADHD, but occurs in about half of ADHD patients. All of the ADHD patients in this study performed poorly on tests of executive function. “Once you have executive function problems, they seem to hang in there,” says Gabrieli, who is a member of the McGovern Institute.
The researchers now plan to investigate how ADHD medications influence the brain’s default mode network, in hopes that this might allow them to predict which drugs will work best for individual patients. Currently, about 60 percent of patients respond well to the first drug they receive.
“It’s unknown what’s different about the other 40 percent or so who don’t respond very much,” Gabrieli says. “We’re pretty excited about the possibility that some brain measurement would tell us which child or adult is most likely to benefit from a treatment.”
The research was funded by the Poitras Center for Affective Disorders Research at the McGovern Institute.
Yinqing Li: Solving the Connectome
Yinqing Li is a graduate student in Feng Zhang’s lab and a McGovern Institute Friends Fellow. His career goal is to “solve the connectome.”
Leah Acker: Engineering the Brain
Leah Acker is a McGovern Institute Friends Fellow who earned her PhD working in the labs of Bob Desimone and Ed Boyden. Leah’s projects involve the invention and application of new technologies for less-invasive neuromodulation, and the study of optogenetic control of brain circuits.
Patrick J. McGovern Memorial Service
Illuminating neuron activity in 3-D
Researchers at MIT and the University of Vienna have created an imaging system that reveals neural activity throughout the brains of living animals. This technique, the first that can generate 3-D movies of entire brains at the millisecond timescale, could help scientists discover how neuronal networks process sensory information and generate behavior.
The team used the new system to simultaneously image the activity of every neuron in the worm Caenorhabditis elegans, as well as the entire brain of a zebrafish larva, offering a more complete picture of nervous system activity than has been previously possible.
“Looking at the activity of just one neuron in the brain doesn’t tell you how that information is being computed; for that, you need to know what upstream neurons are doing. And to understand what the activity of a given neuron means, you have to be able to see what downstream neurons are doing,” says Ed Boyden, an associate professor of biological engineering and brain and cognitive sciences at MIT and one of the leaders of the research team. “In short, if you want to understand how information is being integrated from sensation all the way to action, you have to see the entire brain.”
The new approach, described May 18 in Nature Methods, could also help neuroscientists learn more about the biological basis of brain disorders. “We don’t really know, for any brain disorder, the exact set of cells involved,” Boyden says. “The ability to survey activity throughout a nervous system may help pinpoint the cells or networks that are involved with a brain disorder, leading to new ideas for therapies.”
Boyden’s team developed the brain-mapping method with researchers in the lab of Alipasha Vaziri of the University of Vienna and the Research Institute of Molecular Pathology in Vienna. The paper’s lead authors are Young-Gyu Yoon, a graduate student at MIT, and Robert Prevedel, a postdoc at the University of Vienna.
High-speed 3-D imaging
Neurons encode information — sensory data, motor plans, emotional states, and thoughts — using electrical impulses called action potentials, which provoke calcium ions to stream into each cell as it fires. By engineering fluorescent proteins to glow when they bind calcium, scientists can visualize this electrical firing of neurons. However, until now there has been no way to image this neural activity over a large volume, in three dimensions, and at high speed.
Scanning the brain with a laser beam can produce 3-D images of neural activity, but it takes a long time to capture an image because each point must be scanned individually. The MIT team wanted to achieve similar 3-D imaging but accelerate the process so they could see neuronal firing, which takes only milliseconds, as it occurs.
The new method is based on a widely used technology known as light-field imaging, which creates 3-D images by measuring the angles of incoming rays of light. Ramesh Raskar, an associate professor of media arts and sciences at MIT and an author of this paper, has worked extensively on developing this type of 3-D imaging. Microscopes that perform light-field imaging have been developed previously by multiple groups. In the new paper, the MIT and Austrian researchers optimized the light-field microscope, and applied it, for the first time, to imaging neural activity.
With this kind of microscope, the light emitted by the sample being imaged is sent through an array of lenses that refracts the light in different directions. Each point of the sample generates about 400 different points of light, which can then be recombined using a computer algorithm to recreate the 3-D structure.
“If you have one light-emitting molecule in your sample, rather than just refocusing it into a single point on the camera the way regular microscopes do, these tiny lenses will project its light onto many points. From that, you can infer the three-dimensional position of where the molecule was,” says Boyden, who is a member of MIT’s Media Lab and McGovern Institute for Brain Research.
Prevedel built the microscope, and Yoon devised the computational strategies that reconstruct the 3-D images.
Aravinthan Samuel, a professor of physics at Harvard University, says this approach seems to be an “extremely promising” way to speed up 3-D imaging of living, moving animals, and to correlate their neuronal activity with their behavior. “What’s very impressive about it is that it is such an elegantly simple implementation,” says Samuel, who was not part of the research team. “I could imagine many labs adopting this.”
Neurons in action
The researchers used this technique to image neural activity in the worm C. elegans, the only organism for which the entire neural wiring diagram is known. This 1-millimeter worm has 302 neurons, each of which the researchers imaged as the worm performed natural behaviors, such as crawling. They also observed the neuronal response to sensory stimuli, such as smells.
The downside to light field microscopy, Boyden says, is that the resolution is not as good as that of techniques that slowly scan a sample. The current resolution is high enough to see activity of individual neurons, but the researchers are now working on improving it so the microscope could also be used to image parts of neurons, such as the long dendrites that branch out from neurons’ main bodies. They also hope to speed up the computing process, which currently takes a few minutes to analyze one second of imaging data.
The researchers also plan to combine this technique with optogenetics, which enables neuronal firing to be controlled by shining light on cells engineered to express light-sensitive proteins. By stimulating a neuron with light and observing the results elsewhere in the brain, scientists could determine which neurons are participating in particular tasks.
Other co-authors at MIT include Nikita Pak, a PhD student in mechanical engineering, and Gordon Wetzstein, a research scientist at the Media Lab. The work at MIT was funded by the Allen Institute for Brain Science; the National Institutes of Health; the MIT Synthetic Intelligence Project; the IET Harvey Prize; the National Science Foundation (NSF); the New York Stem Cell Foundation-Robertson Award; Google; the NSF Center for Brains, Minds, and Machines at MIT; and Jeremy and Joyce Wertheimer.
Patrick J. McGovern Memorial Service
Disruptive Innovations in Neuroscience: Alex Shalek
McGovern Institute Spring Symposium 2014
May 2, 2014
Alex Shalek, Harvard University
“Using single cell transcriptomics to explore cellular identity and uncover drivers of cellular behaviors”